G-rich elements, such as GC-box or GT-box, are sequences that bind to transcription factors which have been found in promoter sequences of various genes including house keeping genes as well as tissue specific genes, parentally expressing genes, etc. The G-rich elements are closely related to development and differentiation, in addition to gene expression upon the binding of transcription factors.
Sp1 has been found as a DNA-binding transcription factor that binds to the GC-box of the SV-40 promoter sequence to regulate the transcriptional activity of the promoter (Dynan, W. S., et al., Cell (1983) 35:79-87; Gidoni, D., et al., Nature (1984) 312:409-413). The Sp1 has three zinc finger domains in its C-terminal region and binds to a GC/GT-box through the domains (Kadonaga, J. T., et al., Cell (1987) 51:1079-1090). Moreover, it has been known that the Sp1 has two glutamine-rich regions required for the activation of transcription (Courey, A. J., et al., Cell (1988) 55:887-898), and yet two serine/threonine-rich regions. Transcription factor homologues, Sp2 (Kingsley, C., et al., Mol Cell Biol (1992) 12:4251-4261), Sp3, and Sp4 (Hagen, G., et al., Nucleic Acids Res (1992) 20:5519-5525), with a high homology to the Sp1 are known to exist and they comprise a family. Each transcription factor has three highly conserved zinc finger domains in its C-terminal region, and besides, a glutamine-rich region and/or a serine/threonine-rich region. While the Sp3 and Sp4, similarly to the Sp1, bind to a GC/GT-box (Hagen, G., et al., Nucleic Acids Res. (1992) 20:5519-5525; Hagen, G., et al., EMBO J. (1994) 13:3843-3851), the Sp2 is reported not to bind to a GC-box and rather binds to a GT-box in the Vα promoter region of TCR (Kingsley, C., et al., Mol. Cell. Biol. (1992) 12:4251-4261).
Recently, many transcription factors with high homology to the three zinc finger domains of Sp1 have been reported (Philipsen, S., et al., Nucleic Acids Res. (1999) 27:2991-3000). As in the case with Sp1, they all have been shown to have three zinc finger domains in its C-terminal regions and bind to a GC/GT-box; however, other regions share only a low homology with the Sp-family and do not have a glutamine-rich region that functions as a transcription activation region in Sp1.
These GC/GT-box binding transcription factors have been known to enhance or repress the transcriptional activity, and thus, are considered to regulate gene expression in various cells during development, differentiation, and such. Such characteristics of the GC/GT-box binding transcription factors described above presently make them remarkable as targets in developing therapeutic agents.